Developments in fluoropyrimidine therapy for gastrointestinal cancer.

The combination of 5-fluorouracil and leucovorin is the standard treatment in metastatic colorectal cancer and in Dukes' C colon cancer. There is, however, no agreement on the method for administration in metastatic colorectal cancer. Several new studies published in 1998 suggest that infusional 5-fluorouracil gives a higher response rate and better toxicity profile compared with a standard bolus 5-fluorouracil/leucovorin regimen. The median survival rate, however, is not different. Several new active drugs are being developed for advanced colorectal cancer. It has not yet been shown that these drugs as single agents are superior to an optimal 5-fluorouracil regimen. Combination trials of 5-fluorouracil/leucovorin with oxaliplatin, CPT-11 and raltitrexed are ongoing, and it can be expected that several of these combinations will be more active than 5-fluorouracil/leucovorin. The challenge for the future will be to show the most active combination and the best sequence of these combinations. The development of the orally administered fluoropyrimidines was rapid in 1998. Randomized studies comparing UFT, capecitabine, and eniluracil plus 5-fluorouracil with 5-fluorouracil/leucovorin are ongoing.